What is the effect of Dapagliflozin (Canagliflozin) in diabetic patients with normal renal function?

From the Guidelines

Dapagliflozin is recommended for patients with type 2 diabetes and normal renal function as part of their glucose-lowering regimen, due to its benefits in reducing cardiovascular risk and improving outcomes, as evidenced by the most recent and highest quality study 1.

Benefits of Dapagliflozin

The standard dosage of dapagliflozin is 10 mg once daily, taken orally in the morning with or without food. For patients with type 2 diabetes who have normal kidney function (eGFR ≥45 mL/min/1.73m²), dapagliflozin offers multiple benefits beyond glucose control, including:

• Weight reduction (typically 2-3 kg)
• Modest blood pressure lowering (3-5 mmHg systolic)
• Cardiovascular protection, with a reduced risk of hospitalization for heart failure or cardiovascular death, as shown in the DAPA-HF trial 1

Mechanism of Action

The medication works by inhibiting sodium-glucose cotransporter-2 (SGLT2) in the proximal tubules of the kidneys, which increases urinary glucose excretion and reduces blood glucose levels independent of insulin.

Potential Side Effects

Patients should be advised about potential side effects, including:

• Genital mycotic infections
• Urinary tract infections
• Volume depletion It's essential to maintain adequate hydration while taking this medication. Dapagliflozin should be temporarily discontinued during periods of reduced oral intake or significant illness that may increase the risk of volume depletion.

Monitoring and Dose Adjustment

Regular monitoring of renal function is recommended, even in patients who start with normal kidney function, as changes in renal status may necessitate dose adjustment or discontinuation. The most recent study 1 supports the use of dapagliflozin in patients with type 2 diabetes and normal renal function, with a reduced risk of cardiovascular events and improved outcomes.

From the FDA Drug Label

The safety and effectiveness of DAPAGLIFLOZIN TABLETS for glycemic control in type 2 diabetes mellitus have not been established in pediatric patients less than 10 years of age In patients ≥65 years of age, a higher proportion of patients treated with dapagliflozin for glycemic control had adverse reactions of hypotension Dapagliflozin was evaluated in 4304 adult patients with chronic kidney disease (eGFR 25 to 75 mL/min/1.73 m2) in the DAPA-CKD trial. Dapagliflozin was also evaluated in 1926 adult patients with an eGFR of 30 to 60 mL/min/1. 73 m2 in the DAPA-HF trial. Patients with diabetes and renal impairment using dapagliflozin may be more likely to experience hypotension and may be at higher risk for acute kidney injury secondary to volume depletion. By inhibiting SGLT2, dapagliflozin reduces reabsorption of filtered glucose and thereby promotes urinary glucose excretion

The effect of Dapagliflozin in diabetic patients with normal renal function is that it reduces reabsorption of filtered glucose and promotes urinary glucose excretion by inhibiting SGLT2.

• Key benefits include:
  • Improved glycemic control
• Key risks include:
  • Hypotension
  • Acute kidney injury secondary to volume depletion
  • Genital mycotic infections
  • Ketoacidosis
  • Increase in hematocrit and low-density lipoprotein cholesterol 2

From the Research

Effects of Dapagliflozin on Diabetic Patients with Normal Renal Function

• Dapagliflozin reduces renal glucose reabsorption, leading to urinary glucose excretion and a reduction in blood glucose levels 3, 4, 5.
• The efficacy of dapagliflozin is independent of insulin secretion and action, making it a complementary therapy when used in combination with other antidiabetic drugs 3, 4, 5.
• Dapagliflozin has been shown to significantly reduce glycosylated haemoglobin values and fasting plasma glucose levels compared with placebo in patients with type 2 diabetes 3, 4, 5.
• Dapagliflozin is also associated with reductions in body weight, which are statistically superior to placebo or active comparators 3, 4, 5.
• The drug has a low propensity to cause hypoglycaemia, especially when used alone or in combination with metformin 3, 4, 5.

Safety and Tolerability

• Dapagliflozin is generally well tolerated in clinical trials, with the frequency of most adverse events similar to that seen with placebo 3, 6, 4.
• Events suggestive of genital infections and urinary tract infections occurred more frequently among dapagliflozin than placebo recipients 3, 6, 4.
• Dapagliflozin may decrease glomerular filtration rate (GFR), especially in elderly patients and patients with impaired renal function, and renal function should be monitored before initiation of dapagliflozin 6, 4.

Comparison with Other Treatments

• Dapagliflozin was noninferior to glipizide in terms of glycaemic control after 52 weeks, when used as add-on therapy in patients with type 2 diabetes that was inadequately controlled with metformin 3.
• Dapagliflozin has been shown to reduce weight and blood pressure, but does not improve glycemic control in patients with moderate renal impairment 7.